Tumor imaging quantification is critical for diagnosis, staging, and treatment evaluation, and multi-detector CT (MDCT) is the clinical imaging modality commonly used for patients diagnosed with hepatic malignancy because of its relatively low cost and wide availability. Conventional tumor quantification using either linear or volumetric measurement has demonstrated significant limitations in the evaluation of malignant liver tumors such as for hepatocellular carcinoma (HCC) when being treated with targeted antiangiogenic therapies or locoregional therapies because changes in overall tumor size do not necessarily reflect tumor response to therapy. This leads to an unmet clinical demand to develop a functional tumor quantification biomarker for effective and accurate assessment of treatment response for liver cancer patients. The goal of this STTR project is to expand development of our functional tumor quantitative imaging biomarker (QIB), named hepatic tumor viability (HTV), for automated quantification of tumor viability of HCC using contrast-enhanced multi-phase hepatic MDCT images. The proposed HTV tool will be built upon existing technologies for quantitative imaging analysis of liver and liver tumors developed on the software platform ?3DQI? in the 3D Imaging Lab at Massachusetts General Hospital (MGH), and will be evaluated using the MDCT datasets of 400 patients with advanced HCC treated with antiangiogenic therapies and trans-arterial chemoembolization (TACE) therapies collected at MGH Cancer Center. The specific aims of this Phase II project are: (1) Development of HTV biomarker: We will continue to enhance the HTV biomarker developed in our Phase I project to improve the accuracy of HCC tumor segmentation using machine-learning classifiers, and to expand the four-phase MDCT imaging protocol developed in Phase I to include that of three-phase MDCT by omitting pre-contrast imaging for flexible adoption in clinical practice, (2) Evaluation of HTV biomarker: We will integrate the HTV biomarker into our 3DQI platform to conduct a clinical study to evaluate the accuracy and clinical performance of the proposed HTV biomarker in the assessment of treatment response by assessing 400 advanced HCC cases treated with antiangiogenic and TACE therapies collected at MGH Cancer Center, and (3) Preparation of FDA 510(k) clearance submission: We will establish the quality management system for 3DQI/Liver to meet FDA regulation, and prepare the required documentation for FDA 510(k) clearance submission. This aim is important for the long-term project goal of clinical translation of advanced QIBs developed on the 3DQI/Liver platform for tumor monitoring and response assessment of varied hepatic diseases on both CT and MR images. The successful development and validation of the proposed HTV biomarker will have a high clinical impact by providing a more effective and accurate tumor quantification tool compared to conventional size-based methods for reliable assessment of tumor progression and evaluation of treatment response for patients with HCC.